Examples of methods for treating diseases using nucleic acid drugs include antisense therapies, antigene therapies, aptamer-based therapies, siRNA-based therapies, and the like. Of these, the antisense therapies are approaches for treating or preventing diseases, involving inhibiting a translation process of pathogenic RNAs by externally introducing oligonucleotides (antisense strands) that are complementary to disease-associated mRNAs to form double strands. The siRNA-based therapies are similar to the antisense therapies, involving inhibiting translation from mRNAs to proteins by administering double-stranded RNAs into a living body. Meanwhile, the antigene therapies suppress transcription from DNAs to RNAs by externally introducing triplex-forming oligonucleotides corresponding to DNA sites that are to be transcribed into pathogenic RNAs. Since aptamers are short nucleic acid molecules (oligonucleotides), they function as being bound to biological components such as disease-associated proteins.
Although various artificial nucleic acids have been developed as materials for such nucleic acid drugs, no ideal molecule has been found yet. Examples of the materials developed for nucleic acid drugs to date include phosphorothioate (S—PO3) oligonucleotide (S-oligo), 2′,4′-bridged nucleic acid (BNA)/2′,4′-locked nucleic acid (LNA) (Patent Documents 1 to 4 and Non-Patent Documents 1 to 4), and the like. S-oligo is commercially available in the United States as an antisense drug for cytomegalovirus. S-oligo has a high nuclease resistance, but is problematic and needs improvement in that its binding affinity to the target nucleic acid strands is low. 2′,4′-BNA/LNA developed to date has a high binding affinity to the target nucleic acid strands, and provides the most promising molecules as the materials for the future nucleic acid drugs. However, there is still room for improvement in that the nuclease resistance is not sufficient and the stability in a living body is poor.